This proposal centers about the cellular mechanisms involved in resistance to gastric injury. Techniques are to be refined for preparing highly enriched fractions of surface epithelial cells from canine fundic mucosa with the goal of reconstituting epithelial monolayers in short-term nonreplicating culture. Culture efforts will be aimed at maintaining cellular differentiation. Differentiation will be monitored by morphological studies with mucous stains, electron microscopy and immunoflourescence for blood group substances, which are present on cells from many of the animals. Initial studies indicate that these cells in culture for m a polarized monolayer capable of supporting a potential difference of up ot 35 mV. Studies are planned to characterize the ions being transported and the factors regulating those transport rates. Bicarbonate secretion will be sought using titration. Studies of the factors regulating mucus secretion are planned, with mucus secretion being measured by use of a glucosamine assay and labelled precursor studies. Attempts will be made to establish a model for the cellular aspects of in vitro cytoprotection, looking for such indices as morphological change or a change in transport function or K+ loss exposure to ulcerogenic factors. Emphasis will be placed upon exploring the hypothesis that prostaglandins may enchance resistance to an ulcerogen by acting directly on the surface epithelial cell. Prostaglandin secretion will also be studied, asking the questions of what factors may influence prostaglandin production rate by these cells. The long range goals are to understand the role of the surface epithelial cell in resistance to acid peptic injury in elucidating possible mechanisms by which the defense may break down.